The present invention is concerned with antibacterial 9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin D, pharmaceutically-acceptable salts thereof, and intermediates useful in the preparation thereof from erythromycin D and certain of its esters.
Erythromycin D is a known macrolide antibiotic, having the formula (I), was originally isolated ##STR1## by Majer et al., J. Am. Chem. Soc., 99, pp. 1620-1622, (1977) as a trace component from an industrial erythromycin A purification side stream. More recently, a practical preparation of erythromycin D by direct fermentation has become available. Celmer et al., copending U.S. patent application Ser. No. 367,820, filed Apr. 12, 1982. That fermentation method is also fully disclosed in the Preparation section below.
The present therapeutic compound, which is of the formula (III) below, is structurally related to the previously reported erythromycin A derivative of the formula (III), the subject of British patent application No. 2,094,293, as well as of Bright, copending U.S. patent application Ser. No. 399,401, filed July 19, 1982, now abandoned. In that British application, the compound of the formula (III) is named as the Nmethyl derivative of "11-aza-10-deoxo-10-dihydroerythromycin A", a name coined earlier by Kobrehel et al., U.S. Pat. No. 4,328,334 for the precursor compound of the formula (V). For the latter ring expanded (homo), aza (nitrogen substituted for carbon) erythromycin A derivative, we prefer the name 9-deoxo-9a-aza-9a-homoerythromycin A. That compound could also be named as a 10-aza-14-hexadecanolide derivative. ##STR2## (II) R=methyl, R.sup.a =R.sup.b =hydrogen (III) R=methyl, R.sup.a =hydroxy, R.sup.b =methyl,
(IV) R=hydrogen, R.sup.a =R.sup.b =hydrogen, PA1 (V) R=hydrogen, R.sup.a =hydroxy, R.sup.b =methyl.